Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 June - 14 July 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
in compliance with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 Dec 2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
(Crl:CD(SD)), SPF
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ORIENTBIO INC., Republic of Korea
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 183.9 - 232.3 g
- Fasting period before study: animals were fasted overnight prior to administration
- Housing: individual in wire mesh cages. Cages were washed every two weeks in a cage washer and sterilized by an autoclave.
- Diet: pellet diet Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C (Envigo RMS. Ltd., U.S.A., lot No. 2918C-020816MA), ad libitum
- Water: tap water, ad libitum (analysis was performed)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.6 - 24.1
- Humidity (%): 43.8 - 70.0
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/ 12

IN-LIFE DATES: From: 14 June TO: 28 June 2016

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 60 and 400 mg/mL
- Amount of vehicle (if gavage): 5.0 mL per kg bw
- Lot/batch no. (if required): MKBV2080V

MAXIMUM DOSE VOLUME APPLIED: 5.0 mL per kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose level for this study was selected at 300 mg/kg bw because there was no available toxicity information on the test substance.
Doses:
300 mg/kg bw and 2000 mg/kg bw
No. of animals per sex per dose:
6 females per dose
Control animals:
no
Remarks:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On Day 0, all animals were observed once within 30 minutes and once each at 1, 2, 4 and 6 hours after dosing. From the next day of dosing (from Day 1 to Day 14), the animals were observed once daily. All animals were weighed on Days 0 (before dosing), 1, 3, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights, complete gross postmortem examinations
Statistics:
Mean values and standard deviations were calculated for body weights.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 is a cut-off value obtained from flow-chart of OECD 423 (Annex 2c)
Mortality:
No mortality occurred during the study period.
Clinical signs:
Group 1: 300 mg/kg bw: No clinical abnormalities were observed in any animal.
Group 2: 300 mg/kg bw: No clinical abnormalities were observed in any animal.
Group 3: 2000 mg/kg bw step 1: On Day 0, salivation was observed in all 3 animals after 30 minutes lasting up to 2 hours. After 6 hours abnormal gait was observed in all 3 animals. On day 1, a decrease in fecal volume was observed in 1 of 3 animals.
Group 4: 2000 mg/kg bw step 2: On Day 0, salivation was observed in 1 of 3 animals after 30 minutes lasting up to 1 hour. After 6 hours abnormal gait was observed in 1 of 3 animals. On day 1, a decrease in fecal volume was observed in 2 of 3 animals. Furthermore 1 of 3 animals showed a soiled perineal region on day 1. From Day 2 to Day 14, no clinical signs were observed in any of the animals.
Body weight:
Normal body weight gains was observed in all animals at 300 mg/kg.
A tendency for suppression of body weight gain was observed in three animals at 2000 mg/kg on Day 1. Then, normal body weight gain was observed in these animals from Day 3. Therefore, this change was considered to be a test substance-related effect.
Gross pathology:
No abnormal morphological findings were observed in any animal at 300 and 2000 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
other: not classified
Conclusions:
CLP: not classified
Executive summary:

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 423 and in compliance with GLP (2016). Based on lacking toxicity information on the test substance, the starting dose was selected to be 300 mg/kg bw via gavage, tested in 3 female rats. As no mortality or clinical signs occurred the test was performed again at a dose of 2000 mg/kg bw. No mortality occurred at this dose too.

Thus, a LD50 value > 5000 mg/kg bw was found in this study.